Regulation of P2X2 Receptors by the Neuronal Calcium Sensor VILIP1
Regulation of P2X2 Receptors by the Neuronal Calcium Sensor VILIP1
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DOI：
10.1126/scisignal.1162329
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发表时间：
2008-10-14
影响因子：
7.3
通讯作者：
Khakh, Baljit S.
中科院分区：
文献类型：
--
作者：
Chaumont, Severine;Compan, Vincent;Khakh, Baljit S.
细胞外三磷酸腺苷（ATP）激活P2 X受体，参与多种生理功能。使用蛋白质组学方法，我们确定了神经元钙传感器VILIP 1与P2 X2受体相互作用。我们发现VILIP 1在体外和体内与P2 X2受体形成信号复合物，并调节P2 X2受体对ATP的敏感性、峰值响应、表面表达和扩散。VILIP 1组成型结合P2 X2受体，并显示增强的相互作用，在激活和钙依赖性的方式，由于其结合片段在P2 X2受体的曝光。VILIP 1-P2 X2相互作用在已知触发P2 X2受体激活的动作电位放电条件下也在海马神经元中增强。因此，我们的数据揭示了一个以前未被认识到的功能的神经元钙传感器蛋白VILIP 1和ATP依赖性P2 X受体信号的神经元钙传感器的调节机制。
Extracellular adenosine triphosphate (ATP) activates P2X receptors, which are involved in diverse physiological functions. Using a proteomic approach, we identified the neuronal calcium sensor VILIP1 as interacting with P2X2 receptors. We found that VILIP1 forms a signaling complex in vitro and in vivo with P2X2 receptors and regulates P2X2 receptor sensitivity to ATP, peak response, surface expression, and diffusion. VILIP1 constitutively binds to P2X2 receptors and displays enhanced interactions in an activation- and calcium-dependent manner owing to exposure of its binding segment in P2X2 receptors. VILIP1-P2X2 interactions are also enhanced in hippocampal neurons during conditions of action potential firing known to trigger P2X2 receptor activation. Our data thus reveal a previously unrecognized function for the neuronal calcium sensor protein VILIP1 and a mechanism for regulation of ATP-dependent P2X receptor signaling by neuronal calcium sensors.